Neurons containing the sex hormone, gonadotropin-releasing hormone (GnRH), are found in the nasal cavity along the nervus terminalis. The PI has preliminary evidence that the nervus terminalis secretes GnRH into the nasal cavity to modulate chemosensory transduction processes. In humans, GnRH nasal sprays are being tested to treat a number of diseases and disorders including cancers, endometriosis, and infertility. Possible side effects of these treatments on chemoreception have not been identified. Nasal surgeries performed to correct structural defects may disrupt the GnRH-containing nerve. The clinical significance of interfering with GnRH projections to nasal structures is not known. With a better basic understanding of GnRH function in the nasal cavity, we can better predict how some of these clinical manipulations may affect chemosensory functioning and/or its consequential effects on reproduction. The long-term objectives of this research are to 1) understand how GnRH interacts with the nasal chemosensory systems, 2) understand what factors cause intranasal GnRH release, and 3) determine the clinical significance of interfering with the nasal GnRH system. The main goal of this research proposal is to identify, in the nasal cavity, the route by which GnRH accesses the GnRH receptors. The PI's preliminary evidence suggests that GnRH receptors exist on the dendrites of chemoreceptive neurons. However, the GnRH processes of the nervus terminalis extend only into the lamina propria. With tight junctions separating the surface of the epithelium from the underlying lamina propria, it is unlikely that GnRH diffuses to the surface of the epithelium. The mechanism by which GnRH accesses the GnRH receptors on the olfactory dendritic processes will be determined by this research. The PI's preliminary evidence suggests that GnRH accesses the chemosensory dendrites via mucous from nasal glands. Nasal glands and the overlying mucous in mammals and amphibians are immunopositive for GnRH. Whether nasal gland cells synthesize GnRH or take up GnRH from local nervus terminalis fibers will be tested by performing in situ hybridization, and quantitative autoradiography following incubation in exogenous GnRH, respectively. Pharmacological experiments will be performed to study GnRH release from nasal glands using quantitative autoradiography of the tissue and radioassays of the incubating solutions. These experiments will provide the field with new insight into hormonal modulation of olfaction.